This K01 research and training award advances the long-term goal of integrating behavioral and biomedical strategies for preventing HIV among men who have sex with men (MSM). The proposed training will enable the PI to develop the skills needed for an independent research career in this field. The research plan focuses on the behavioral impacts of antiretroviral pre-exposure prophylaxis (PrEP), an emerging biomedical strategy for HIV prevention. PrEP is anticipated to be partially efficacious for preventing new infections, and models based on early study data suggest that PrEP may reduce HIV incidence among MSM. However, PrEP's actual effectiveness will depend on users' behaviors, and uncertainty about these behaviors hampers efforts to plan for scale-up. We focus on two behaviors: PrEP initiation - starting to use PrEP; and risk compensation - the possibility that users will take more HIV-related risks on the belief that they are protected from infection. Exploratory research suggests that expectations of PrEP efficacy will influence each behavior, but we lack conceptual models of either behavior among MSM. There is also concern about how these behaviors might be influenced by different strategies for describing PrEP's efficacy. We address these gaps, focusing on MSM in Providence, RI. Phase 1 will use focus groups and individual qualitative interviews to explore psychosocial and contextual factors likely to influence PrEP initiation and risk compensation. Phase 2 will draw on these findings and prior work in biomedical HIV prevention to develop a conceptual model of each behavior, and quantitative outcomes assessing willingness to use PrEP, attitudes about risk compensation, and expectations of PrEP's efficacy. Phase 3 will rely on message framing principles to conduct a randomized trial of two strategies for communicating with MSM about PrEP, one using success-based messages (emphasizing PrEP's likelihood of preventing HIV), and one using failure-based messages (using identical estimates of efficacy, but emphasizing PrEP's likelihood of failure). We hypothesize that participants receiving success-based messages will be more willing to use PrEP, but will have higher expectations of efficacy and more permissive attitudes toward risk compensation. Our findings may generalize to other partially efficacious HIV prevention strategies, such as vaccines and circumcision. Future research plans include developing behavioral interventions to optimize PrEP use among MSM. To enable the PI to pursue this long-term research agenda, she will work with experienced mentors to build four areas of expertise: (1) expertise in the behavioral impacts of biomedical HIV prevention, including links among PrEP, post-exposure prophylaxis, vaccines, microbicides, and circumcision; (2) expertise in health communications and message framing; (3) skills for conducting qualitative research in mixed-methods studies; and (4) skills for conducting quantitative research in mixed-methods studies, including developing outcome measures, implementing trials, and statistically analyzing trial data. This K01 addresses a key priority in HIV prevention science, and it will fully prepare the PI for an independent research career in the field. PUBLIC HEALTH RELEVANCE: Antiretroviral pre-exposure prophylaxis (PrEP) - providing antiretroviral medications to HIV-negative people before they engage in HIV risk behaviors - is a promising new biomedical option being developed for HIV prevention, but uncertainty about PrEP's behavioral impacts impedes preparations for using it as a public health strategy. We will address this uncertainty through formative research on two behaviors that will influence how well PrEP works in practice: PrEP initiation (whether people decide to use PrEP medications) and risk compensation (the possibility that people will increase their HIV risk behaviors once they are using PrEP). The outcomes of our study will enable the development of behavioral interventions to encourage effective PrEP use among men who have sex with men, who are a national priority for HIV prevention.